BACKGROUND: The cardiodepressor Bezold-Jarisch reflex (BJR) in acute inferior myocardial infarction (AMI) is traditionally considered as an indicator of successful thrombolysis. HYPOTHESIS: The study aim was to elucidate the role of the autonomic nervous system in the pathogenesis of a BJR response in patients with AMI by tracing spectral profiles of heart rate variability (HRV). METHODS: We studied 32 patients who presented with BJR after starting intravenous thrombolysis for an inferior AMI. Spectral components of HRV were analyzed over the three specific 5-min periods preceding and following reflex activation. Clinically, the occurrence of BJR was correlated with the outcome of thrombolysis to achieve timely reperfusion and sustained coronary artery patency. RESULTS: The BJR was associated with early reperfusion in 94% of the patients, and with benign transient bradyarrhythmias and patent Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow right coronary arteries in 89% of the patients. Spectral analysis revealed a characteristic pattern of a sympathetic predominance with an impending gradual vagal withdrawal up to the onset of BJR, as reflected by progressive increases in low-frequency and reciprocal changes in high-frequency powers. CONCLUSIONS: The BJR in inferior AMI represents a reliable prognosticator of timely reperfusion and sustained coronary patency. Stimulation of vagal afferents in response to sympathetic overactivity may be the underlying pathogenetic mechanism promoting a BJR response.